RO4929097 and Erlotinib Hydrochloride in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT01193881|
Recruitment Status : Terminated
First Posted : September 2, 2010
Last Update Posted : September 29, 2015
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer||Drug: Erlotinib Hydrochloride Drug: Gamma-Secretase Inhibitor RO4929097 Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Addition of the Gamma-Secretase Inhibitor RO4929097 to Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
Experimental: Treatment (erlotinib, RO4929097)
Patients receive erlotinib hydrochloride PO QD on days 1-21 and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Erlotinib Hydrochloride
Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Incidence of adverse events assessed using NCI CTCAE version 4.0 (Dose escalation phase) [ Time Frame: Within 30 days of last drug dose ]
- Maximum-tolerated dose of RO4929097 and erlotinib hydrochloride defined as the highest dose tested causing dose limiting toxicity in < 2/6 patients assessed using National Cancer Institute (NCI) CTCAE version 4.0 (Dose escalation phase) [ Time Frame: At least 3 weeks after day 1 of course 1 ]
- Percentage of change in expression of Notch and other tumor and blood biomarkers (Expansion cohort) [ Time Frame: Baseline to 6 weeks ]The differences before and after treatment will be assessed using a paired-t test on the log-transformed tumor sizes and a Wilcoxon signed-rank test.
- Percentage of tumor shrinkage (Expansion cohort) [ Time Frame: Up to 6 weeks ]Will be correlated with response and baseline expression of biomarkers. The differences before and after treatment will be assessed using a paired-t test on the log-transformed tumor sizes and a Wilcoxon signed-rank test.
- Response rate by RECIST 1.1 (Expansion cohort) [ Time Frame: Up to 12 weeks ]
- Time to progression (Expansion cohort) [ Time Frame: Up to 12 weeks ]Will be correlated with baseline expression or biomarkers.
- Efficacy of this combination in unselected patients and in patients with intrinsic or acquired erlotinib resistance (Dose escalation phase) [ Time Frame: Up to 12 weeks ]
- Host Notch pathway gene polymorphisms [ Time Frame: Up to 6 weeks ]Correlations between Notch pathway gene polymorphisms and tumor and blood biomarkers will be assessed. Correlations between Notch pathway gene polymorphisms and tumor shrinkage/response on therapy will also be assessed.
- Pre-therapy tumor expression of Notch and other tumor and blood biomarkers (Dose escalation phase) [ Time Frame: Baseline ]Exploratory assessments of correlations of tumor shrinkage and response on the combination with pre-therapy tumor expression of Notch and other tumor and blood biomarkers will be conducted.
- Stem cell markers [ Time Frame: Up to 6 weeks ]Correlations between Notch pathway markers and stem cell markers will be assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01193881
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Don Gibbons||M.D. Anderson Cancer Center|